The Enzymology of Oxygen Sensing

When oxygen becomes limiting (hypoxia), mammalian cells respond by increasing the transcription of genes that enhance oxygen delivery or that facilitate metabolic adjustment to reduced oxygen availability. This adaptive response is mediated by hypoxia-inducible factor (HIF), a transcription factor that is stable under hypoxic conditions but is targeted for degradation in the presence of oxygen when a specific proline residue in the protein becomes hydroxylated. Bruick and McKnight have identified a family of evolutionarily conserved enzymes, HIF prolyl hydroxylases, that are responsible for this posttranslational modification. Discovery of these enzymes could open up new therapeutic possibilities for the many diseases in which hypoxia plays a crucial role, such as ischemic heart disease and stroke.